Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia

Briot, Thomas; Roger, Émilie; Lautram, Nolwenn; Verger, Alexis; Clavreul, Anne; Lagarce, Frédéric

doi:10.2147/ijn.s147659

Cited by 21 publications

(21 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Oral AZA (CC-486) has been assessed in a Phase 1 trial [111] for AML and MDS, and a Phase 3 trial in low-risk MDS is ongoing (NCT01566695), showing the interest in the possible oral administration of such agents. DEC encapsulation in lipid-based NPs for oral administration is currently under investigation [112][113][114]. For example, after DEC solubilization in Transcutol® HP and Precirol® ATO5, followed by homogenization under high pressure (500-1000 bar) in cold conditions, particles of 116 nm were obtained by Neupane et al [113].…”

Section: Lipid-based Nanoparticlesmentioning

confidence: 99%

“…An ex vivo permeation study (on an ileum segment) was performed and a fourfold increase in DEC in vitro permeability was observed compared with a DEC solution [112]. When DEC was loaded into an NLC formulation of 30 nm obtained using a low-energy phase inversion process, its cytotoxicity on two AML cell lines (HEL and HL-60) was enhanced by a factor of 1.5 on HEL cells and 1.8 on HL-60 cells compared with free DEC [114]. Moreover, the apparent permeability of an NCL formulation across a Caco-2 cells monolayer was enhanced by a factor of over nine.…”

Section: Lipid-based Nanoparticlesmentioning

confidence: 99%

See 1 more Smart Citation

Advances in treatment formulations for acute myeloid leukemia

Briot

Roger

Thépot

et al. 2018

Drug Discovery Today

Self Cite

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is the most common cause of leukemia-related mortality. The combination of cytarabine and anthracycline has been the gold standard of treatment over the past 40 years, but the distribution of the drugs in the body leads to severe adverse effects. Poor prognosis of older patients with AML is the consequence not only of comorbidities, but also of chemoresistance resulting from frequent secondary AML. Numerous strategies using nanotechnologies are in development to improve drug targeting, pharmacokinetics, administration route, chemoresistance, and adverse effects generally observed. Among the four new drugs approved for AML by the US Food and Drug Administration (FDA) in 2017, Vyxeos is a novel liposomal formulation of historical AML drugs. Here, we review current AML treatments and discuss how the development of new formulations will change the therapeutic armamentarium.

show abstract

Section: Lipid-based Nanoparticlesmentioning

confidence: 99%

Section: Lipid-based Nanoparticlesmentioning

confidence: 99%

Advances in treatment formulations for acute myeloid leukemia

Briot

Roger

Thépot

et al. 2018

Drug Discovery Today

Self Cite

View full text Add to dashboard Cite

show abstract

“…An LC-MS/MS method previously published was used. 19 The mobile phase consisted of a mixture of A) 0.1% formic acid in 10 mM ammonium acetate and B) 0.1% formic acid in acetonitrile, in gradient mode ( Table 1). A 3-µm Nucleodur ® HILIC column (Macherey Nagel, Hoerdt, France), containing an ammoniumsulfonic-acid-modified silica, was used with the temperature fixed at 25°C.…”

Section: Determination Of Decitabine Concentrationsmentioning

confidence: 99%

“…18 We were, thus, interested in encapsulating decitabine in these nanocarriers. 19 However, the encapsulation of decitabine alone has only resulted in low-encapsulation yields.…”

Section: Introductionmentioning

confidence: 99%

<p>Di-<em>O</em>-lauroyl-decitabine-lipid nanocapsules: toward extending decitabine activity</p>

Briot¹,

Roger²,

Haidar³

et al. 2019

IJN

Self Cite

View full text Add to dashboard Cite

Background: Acute myeloid leukemia mainly affects adult patients. Complete remission for patients younger than 60 years, who are candidates for standard induction therapy, is achieved in 60%-80% of cases. However, the prognosis is still poor for older patients, who are unfit for intensive chemotherapy, and only a few therapies are available. Hypomethylating agents, such as decitabine, are approved for such patients. The current dosing regimen consists of one administration per day, for 5 days, each 4 weeks. Methods: Here, we present the synthesis of a decitabine prodrug, combined with its encapsulation into a lipid-based nanocapsule formulation. Decitabine (C12) 2 was synthetized, then loaded into nanocapsules. Its stability in phosphate buffer ans human plasma was checked. Its activity was evaluated by Cell proliferation assays and cell-cycle analysis on human erythroleukemia cells. Then its pharmacokinetics was determined on a rat model. Results: Decitabine (C12) 2 was obtained with a yield of 50%. Drug loading into nanocarriers of 27.45±0.05 nm was 5.8±0.5 mg/mL. The stability of decitabine was improved and its activity on leukemia cells was not altered. Finally, pharmacokinetics studies showed a prolonged mean residence time of the drug. Conclusion: Decitabine (C12) 2 as a prodrug showed high encapsulation efficiency, a good stability in plasma with no impact on its activity on leukemia cells and improved pharmacokinetics.

show abstract

“…The nucleoside analog 5-aza-2′-deoxycytidine (decitabine, DAC) is a potent antileukemic agent, currently used in chemotherapy for the treatment of myelodysplastic syndromes (MDS), acute myelodysplastic leukemia (AML), chronic myelogenous leukemia (CML), which is nowadays in clinical trial for other human cancers and sickle cell anemia (Dinardo et al 2019;Briot et al 2017;Issa et al 2004). Besides, there is ample evidence that numerous epigenetic mutations are directly linked with carcinogenesis, such as the commonly identi ed aberrant DNA methylation in AML disorder (Jabbour et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Decitabine bioproduction using a biocatalyst with improved stability by adding nanocomposites

Méndez

Trelles

Rivero

2020

Preprint

View full text Add to dashboard Cite

A novel IDA-LaNDT derivative was able to reach the highest productivity in the biosynthesis of a well-known antitumoral agent called decitabine. However, the combination of two simple and inexpensive techniques such as ionic absorption and gel entrapment with the incorporation of a bionanocomposite such as bentonite significantly improved the stability of this biocatalyst. These modifications allowed the enhancement of storage stability (for at least 18 months), reusability (400 h of successive batches without significant loss of its initial activity), and thermal and solvent stability with respect to the non-entrapped derivative. Moreover, reaction conditions were optimized by increasing the solubility of 5-aza by dilution with dimethylsulfoxide. Therefore, a scale-up of the bioprocess was assayed using the developed biocatalyst, obtaining 221 mg/L.h of DAC. Finally, green parameters were calculated using the nanostabilized biocatalyst, whose results indicated that it was able to biosynthesize DAC by a smooth, cheap, and environmentally friendly methodology.

show abstract

Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia

Abstract: International audienc

Cited by 21 publications

References 44 publications

Advances in treatment formulations for acute myeloid leukemia

Advances in treatment formulations for acute myeloid leukemia

<p>Di-<em>O</em>-lauroyl-decitabine-lipid nanocapsules: toward extending decitabine activity</p>

Decitabine bioproduction using a biocatalyst with improved stability by adding nanocomposites

Contact Info

Product

Resources

About